Research Projects

The proposed project is associated with the chemotherapeutic evaluation of anti-PD-L1 peptide-conjugated prodrug nanoparticles for the targeted lung cancer immunotherapy. In particular, the cytotoxic activity of anti-PD-L1 peptide conjugated histone deacetylase (HDAC) inhibitors (Entinostat, Tacedinaline, Mocetinostat) through cathepsin B-specific cleavable peptide will be investigated in the context of immunogenic cell death by altering the expression profiling of T cells and triggering of anticancer host immune response. It will be the very first time, where such an approach will be taken into account for the treatment of lung carcinoma and optimum targeting of cancer cells will be achieved by cathepsin B specific bioenzyme, particularly over-expressed in lung cancer cells. On the other hand, the normal cells with low cathepsin B expression will remain non-responsive to prodrug nanoparticles. In this project, the toxicological assessment of the prodrug nanoparticles will be carried out to determine the chemotherapeutic dose regimen. Subsequently, the xenograft model of lung cancer will be developed to investigate the chemotherapeutic efficacy of the prodrug nanoparticles. Furthermore, the chemotherapeutic assessment will be performed against resistant lung cancer cell lines to investigate the effect of prodrug nanoparticles in the re-sensitization of cancer cells towards cancer immunotherapy. Most importantly, the elucidation of molecular mechanism will help us in understanding the novel pathways of prodrug nanoparticles mediated cancer immunotherapy through immunogenic cell death in lung carcinoma.

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